6-134227005-A-T

Variant names:

• chr6-134227005-A-T
• rs9493867
• NM_001143676.3:c.286-19574T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143676.3(SGK1):​c.286-19574T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,036 control chromosomes in the GnomAD database, including 748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (748 hom., cov: 32)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 3 publications found

Genes affected

SGK1 (HGNC:10810): (serum/glucocorticoid regulated kinase 1) This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. High levels of expression of this gene may contribute to conditions such as hypertension and diabetic nephropathy. Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143676.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	NM_001143676.3	MANE Select	c.286-19574T>A		intron	N/A	NP_001137148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	ENST00000367858.10	TSL:1 MANE Select	c.286-19574T>A		intron	N/A	ENSP00000356832.5
	SGK1	ENST00000944482.1		c.70-19574T>A		intron	N/A	ENSP00000614541.1
	SGK1	ENST00000461976.2	TSL:4	c.193-19574T>A		intron	N/A	ENSP00000435577.1

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12575 AN: 151918 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0851

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0829 AC: 12598 AN: 152036 Hom.: 748 Cov.: 32 AF XY: 0.0792 AC XY: 5891 AN XY: 74338

African (AFR) AF: 0.166 AC: 6866 AN: 41470

American (AMR) AF: 0.0605 AC: 925 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.0294 AC: 151 AN: 5134

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4822

European-Finnish (FIN) AF: 0.0300 AC: 318 AN: 10588

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0548 AC: 3725 AN: 67966

Other (OTH) AF: 0.0847 AC: 178 AN: 2102

Alfa AF: 0.0129 Hom.: 6

Bravo AF: 0.0907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.45
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9493867; hg19: chr6-134548143;